Using serological measures to estimate influenza incidence in the presence of secular trends in exposure and immuno-modulation of antibody response

Background: Influenza infection is often measured by a fourfold antibody titer increase over an influenza season (ie seroconversion). However, this approach may fail when influenza seasons are less distinct as it does not account for transient effects from recent infections. Here, we present a method to determine seroconversion for non-paired sera, adjusting for changes in individuals’ antibody titers to influenza due to the transient impact of recent exposures, varied sampling times, and laboratory processes. Methods: We applied our method using data for five H3N2 strains collected from 942 individuals, aged 2-90 years, during the first two study visits of the Fluscape cohort study (2009-2012) in Guangzhou, China. Results: After adjustment, apparent seroconversion rates for non-circulating strains decreased while we observed a 20% increase in seroconversion rates to recently circulating strains. When examining seroconversion to the most recently circulating strain (A/Brisbane/20/2007) in our study, participants aged under 18, and over 64 had the highest seroconversion rates compared to other age groups. Conclusions: Our results highlight the need for improved methods when using antibody titers as an endpoint in settings where there is no clear influenza “off” season. Methods, like those presented here, that use titers from circulating and non-circulating strains may be key.